Cholinergic agonists reduce blood pressure in a mouse model of systemic lupus erythematosus

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dc.creatorFairley, Amber S.
dc.creatorMathis, Keisa W.
dc.date.accessioned2022-10-14T16:48:29Z
dc.date.available2022-10-14T16:48:29Z
dc.date.issued2017-04-10
dc.description.abstractIncreased inflammation arising from an abnormal immune response can damage healthy tissue and lead to disease progression. An important example of this is the accumulation of inflammatory mediators in the kidney, which can subsequently lead to hypertension and renal injury. The origin of this inflammation may involve neuro-immune interactions. For example, the novel vagus nerve-to-spleen mechanism known as the "cholinergic anti-inflammatory pathway" controls inflammation upon stimulation. However, if this pathway is dysfunctional, inflammation becomes less regulated and chronic inflammatory diseases such as hypertension may develop. Systemic lupus erythematosus (SLE) is an autoimmune disease with aberrant immune function, increased renal inflammation, and prevalent hypertension. We hypothesized that the cholinergic anti-inflammatory pathway is impaired in SLE and that stimulation of this pathway would protect from the progression of hypertension in SLE mice. Female SLE (NZBWF1) and control (NZW) mice were administered nicotine or vehicle for 7 days (2 mg/kg/day, subcutaneously) in order to stimulate the cholinergic anti-inflammatory pathway at the level of the splenic nicotinic acetylcholine receptor (alpha7-nAChR). Blood pressure was assessed posttreatment. Nicotine-treated SLE mice did not develop hypertension and this lower blood pressure (compared to saline-treated SLE mice) coincided with lower splenic and renal cortical expression of pro-inflammatory cytokines. These data provide evidence that the cholinergic anti-inflammatory pathway is impaired in SLE In addition, these data suggest that stimulation of the cholinergic anti-inflammatory pathway can protect the kidney by dampening inflammation and therefore prevent the progression of hypertension in the setting of SLE.
dc.description.sponsorshipThis study was partially funded by the National Institutes of Health (F32HL114272-01A1 to KWM) while at the University of Mississippi Medical Center and the American Heart Association (14SDG18320033 to KWM) while at the University of North Texas Health Science Center.This study was partially funded by the National Institutes of Health (F32HL114272-01A1 to KWM) while at the University of Mississippi Medical Center and the American Heart Association (14SDG18320033 to KWM) while at the University of North Texas Health Science Center.
dc.identifier.citationFairley, A. S., & Mathis, K. W. (2017). Cholinergic agonists reduce blood pressure in a mouse model of systemic lupus erythematosus. Physiological reports, 5(7), e13213. https://doi.org/10.14814/phy2.13213
dc.identifier.issn2051-817X
dc.identifier.issue7
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31872
dc.identifier.volume5
dc.publisherWiley Periodicals, Inc.
dc.relation.urihttps://doi.org/10.14814/phy2.13213
dc.rights.holder© 2017 The Authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePhysiological Reports
dc.subjectCholinergic anti-inflammatory pathway
dc.subjecthypertension
dc.subjectinflammation
dc.subjectkidney
dc.subjectnicotine
dc.subjectrenal injury
dc.subject.meshAnimals
dc.subject.meshBlood Pressure / drug effects
dc.subject.meshBlood Pressure Determination
dc.subject.meshCholinergic Agonists / pharmacology
dc.subject.meshCholinergic Agonists / therapeutic use
dc.subject.meshCytokines / metabolism
dc.subject.meshDisease Models, Animal
dc.subject.meshDisease Progression
dc.subject.meshFemale
dc.subject.meshHypertension / drug therapy
dc.subject.meshHypertension / metabolism
dc.subject.meshHypertension / physiopathology
dc.subject.meshKidney / drug effects
dc.subject.meshKidney / metabolism
dc.subject.meshLupus Erythematosus, Systemic / drug therapy
dc.subject.meshLupus Erythematosus, Systemic / metabolism
dc.subject.meshLupus Erythematosus, Systemic / physiopathology
dc.subject.meshMice
dc.subject.meshNicotine / pharmacology
dc.subject.meshNicotine / therapeutic use
dc.subject.meshSpleen / drug effects
dc.subject.meshSpleen / metabolism
dc.subject.meshTreatment Outcome
dc.titleCholinergic agonists reduce blood pressure in a mouse model of systemic lupus erythematosus
dc.typeArticle
dc.type.materialtext

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